The overall goal of this program project is the elucidation of the effects of human neurologic disease on brain metabolism. A primary focus of the CORE Proposal is malignant disease, specifically the physiologic and metabolic consequences of hemispheral neoplasms and peritumoral edema. Other major elements of the CORE proposal include (1) the effects of radiation and chemotherapeutic agents on normal brain tissue; (2) the delineation of the intraparenchymal regions of abnormal capillary pemeability; and (3) the determination of regional equilibrium tissue concentrations of phenytoin in noral volunteers and seizure patients. An equaaly important focus of this application is the study of cerebral ammonia metabolism, and the study of cerebral metabolism and physiology in the aged and demented. A proposed collaboration with Rockland Research Institute concerns the relative importance of specific pathways of carbohydrate intermediary metabolism in normal volunteers and psychiatric inpatients. The development of new radiopharmaceuticals and original biochemical and Mathematcal models will proceed pari passu with the application of existing quantitative methods (for the determination of rCBV, rCBF, rCMRO2 and rCMRGlu) to the above mentioned neurological subpopulations.